Birk J B, Wojtaszewski J F P
Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, 13 Universitetsparken, 2100 Copenhagen Ø, Denmark.
J Physiol. 2006 Dec 15;577(Pt 3):1021-32. doi: 10.1113/jphysiol.2006.120972. Epub 2006 Oct 12.
5'AMP-activated protein kinase (AMPK) is a key regulator of cellular metabolism and is regulated in muscle during exercise. We have previously established that only three of 12 possible AMPK alpha/beta/gamma-heterotrimers are present in human skeletal muscle. Previous studies describe discrepancies between total AMPK activity and regulation of its target acetyl-CoA-carboxylase (ACC)beta. Also, exercise training decreases expression of the regulatory gamma3 AMPK subunit and attenuates alpha2 AMPK activity during exercise. We hypothesize that these observations reflect a differential regulation of the AMPK heterotrimers. We provide evidence here that only the alpha2/beta2/gamma3 subunit is phosphorylated and activated during high-intensity exercise in vivo. The activity associated with the remaining two AMPK heterotrimers, alpha1/beta2/gamma1 and alpha2/beta2/gamma1, is either unchanged (20 min, 80% maximal oxygen uptake ) or decreased (30 or 120 s sprint-exercise). The differential activity of the heterotrimers leads to a total alpha-AMPK activity, that is decreased (30 s trial), unchanged (120 s trial) and increased (20 min trial). AMPK activity associated with the alpha2/beta2/gamma3 heterotrimer was strongly correlated to gamma3-associated alpha-Thr-172 AMPK phosphorylation (r(2) = 0.84, P < 0.001) and to ACCbeta Ser-221 phosphorylation (r(2) = 0.65, P < 0.001). These data single out the alpha2/beta2/gamma3 heterotrimer as an important actor in exercise-regulated AMPK signalling in human skeletal muscle, probably mediating phosphorylation of ACCbeta.
5'腺苷酸活化蛋白激酶（AMPK）是细胞代谢的关键调节因子，在运动过程中其在肌肉中受到调节。我们之前已经确定，在人类骨骼肌中仅存在12种可能的AMPKα/β/γ异源三聚体中的三种。先前的研究描述了总AMPK活性与其靶标乙酰辅酶A羧化酶（ACC）β的调节之间的差异。此外，运动训练会降低调节性γ3 AMPK亚基的表达，并减弱运动期间α2 AMPK的活性。我们假设这些观察结果反映了AMPK异源三聚体的差异调节。我们在此提供证据表明，在体内高强度运动期间，只有α2/β2/γ3亚基被磷酸化并激活。与其余两种AMPK异源三聚体α1/β2/γ1和α2/β2/γ1相关的活性要么不变（20分钟，最大摄氧量的80%），要么降低（30秒或120秒短跑运动）。异源三聚体的差异活性导致总α-AMPK活性降低（30秒试验）、不变（120秒试验）和增加（20分钟试验）。与α2/β2/γ3异源三聚体相关的AMPK活性与γ3相关的α-苏氨酸-172 AMPK磷酸化密切相关（r(2)=0.84，P<0.001），与ACCβ丝氨酸-221磷酸化密切相关（r(2)=0.65，P<0.001）。这些数据表明，α2/β2/γ3异源三聚体是人类骨骼肌运动调节的AMPK信号传导中的重要参与者，可能介导ACCβ的磷酸化。
